Problem. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) continue to be a major cause of morbidity and mortality in critically ill patients. Despite recent advances, major questions remain about ways to identify patients at the highest risk for ALI/ARDS, the true incidence and prevalence of ALI/ARDS, the critical factors involved in the pathogenesis of ALI/ARDS, and individual host factors that influence whether patients develop ALI/ARDS. Specific Aims. The specific aims are: 1) to develop clinical prediction tools that provide individual risk assessment for the onset and outcome of lung injury; 2) to determine the incidence and outcome of ALI/ARDS in populations beyond a single institutions; 3) to determine the relationship between inflammatory responses and injury to the lung endothelial and epithelial barriers; and 4) to investigate determinants of host susceptibility that modulate the occurrence of ALI/ARDS in patients at risk. Experimental Approach. We will build on our experience studying the epidemiology of ARDS at Harborview Medical Center and expand our scope to study a population based cohort in King County WA. We will link data from computerized ICU records at 7 national hospitals to construct a detailed database on ALI/ARDS patients. These data, and the resources of the 13 year Seattle SCOR ARDS Registry, will be used to derive and validate clinical prediction tools for lung injury and onset and mortality; and to describe the population incidence and outcomes of lung injury. We will continue to investigate inflammatory responses in the lungs of patients before and after the onset of ARDS, and determine the relationship between inflammatory responses and injury to the endothelial and epithelial barriers of the lungs. Finally, we will investigate genetically determined host factors that might contribute to susceptibility to ALI/ARDS. Importance of the data. These studies will improve our understanding of 1) the epidemiology of ALI and ARDS; 2) the magnitude of the problem (including incidence, mortality, economic burden, and morbidity in survivors) in a population which we believe will be generalizable to the U.S.; 3) the relationship between inflammatory responses and lung injury; and 4) host factors that may modify susceptibility to lung injury.